CA2965034A1 - Combinaison d'un agent immunomodulaire et d'un oligonucleotide antisens - Google Patents
Combinaison d'un agent immunomodulaire et d'un oligonucleotide antisens Download PDFInfo
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- CA2965034A1 CA2965034A1 CA2965034A CA2965034A CA2965034A1 CA 2965034 A1 CA2965034 A1 CA 2965034A1 CA 2965034 A CA2965034 A CA 2965034A CA 2965034 A CA2965034 A CA 2965034A CA 2965034 A1 CA2965034 A1 CA 2965034A1
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Abstract
La présente invention concerne des méthodes de traitement du cancer avec un agent immunomodulateur, tel qu'un anticorps anti-PD-L1 ou un fragment de liaison à l'antigène de celui-ci, et un composé antisens ciblant le gène STAT3 chez un sujet qui en attente d'un tel traitement.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201462068141P | 2014-10-24 | 2014-10-24 | |
| US62/068141 | 2014-10-24 | ||
| PCT/EP2015/074271 WO2016062722A1 (fr) | 2014-10-24 | 2015-10-20 | Association médicamenteuse |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2965034A1 true CA2965034A1 (fr) | 2016-04-28 |
| CA2965034C CA2965034C (fr) | 2023-05-02 |
Family
ID=54347516
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2965034A Active CA2965034C (fr) | 2014-10-24 | 2015-10-20 | Combinaison d'un agent immunomodulaire et d'un oligonucleotide antisens |
Country Status (16)
| Country | Link |
|---|---|
| US (2) | US20190194654A1 (fr) |
| EP (2) | EP3209778B1 (fr) |
| JP (1) | JP6687612B2 (fr) |
| KR (2) | KR20170072928A (fr) |
| CN (2) | CN115920007A (fr) |
| AU (1) | AU2015335029B2 (fr) |
| CA (1) | CA2965034C (fr) |
| DK (1) | DK3209778T3 (fr) |
| ES (1) | ES2727154T3 (fr) |
| HU (1) | HUE043227T2 (fr) |
| IL (2) | IL251813A0 (fr) |
| PL (1) | PL3209778T3 (fr) |
| RU (1) | RU2744841C2 (fr) |
| SG (2) | SG11201703219WA (fr) |
| TR (1) | TR201906415T4 (fr) |
| WO (1) | WO2016062722A1 (fr) |
Families Citing this family (39)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20180056816A (ko) | 2009-05-11 | 2018-05-29 | 베르그 엘엘씨 | 환경대사적 전환인자（조효소 ｑ１０）를 사용한 질환의 치료 방법 |
| JP6092844B2 (ja) | 2011-04-04 | 2017-03-08 | バーグ エルエルシー | 中枢神経系腫瘍の治療方法 |
| NZ713868A (en) | 2013-04-08 | 2021-12-24 | Berg Llc | Treatment of cancer using coenzyme q10 combination therapies |
| SG10201907816RA (en) | 2013-09-04 | 2019-09-27 | Berg Llc | Methods of treatment of cancer by continuous infusion of coenzyme q10 |
| MX360295B (es) * | 2014-05-29 | 2018-10-29 | Medimmune Llc | Proteinas de fusion del ligando de ox40 (ox40l) y sus usos. |
| US11213593B2 (en) | 2014-11-21 | 2022-01-04 | Northwestern University | Sequence-specific cellular uptake of spherical nucleic acid nanoparticle conjugates |
| CA2978942A1 (fr) | 2015-03-13 | 2016-09-22 | Cytomx Therapeutics, Inc. | Anticorps anti-pdl1, anticorps anti-pld1 activables, et leurs procedes d'utilisation |
| KR20180015650A (ko) | 2015-05-07 | 2018-02-13 | 아게누스 인코포레이티드 | 항-ox40 항체 및 이의 사용 방법 |
| EP3322732A2 (fr) | 2015-07-13 | 2018-05-23 | Cytomx Therapeutics Inc. | Anticorps anti-pd-1, anticorps anti-pd-1 activables, et leurs procédés d'utilisation |
| EP3371311B1 (fr) | 2015-11-06 | 2021-07-21 | Orionis Biosciences BV | Protéines chimères bifonctionnelles et leurs utilisations |
| CA3007233A1 (fr) | 2015-12-02 | 2017-06-08 | Agenus Inc. | Anticorps et leurs methodes d'utilisation |
| EP3998281A1 (fr) | 2016-02-05 | 2022-05-18 | Orionis Biosciences BV | Agents de liaison au cd8 |
| US10421811B2 (en) * | 2016-04-25 | 2019-09-24 | Medimmune, Llc | Compositions comprising coformulation of anti-PD-L1 and anti-CTLA-4 antibodies |
| JP7105200B2 (ja) | 2016-05-13 | 2022-07-22 | オリオニス バイオサイエンシズ ビーブイ | 標的突然変異体インターフェロン－ベータおよびその使用 |
| WO2017194782A2 (fr) | 2016-05-13 | 2017-11-16 | Orionis Biosciences Nv | Ciblage thérapeutique de structures non cellulaires |
| US20180021270A1 (en) * | 2016-07-21 | 2018-01-25 | Berg Llc | Methods for the treatment of cancer using coenzyme q10 in combination with immune checkpoint modulators |
| WO2018039629A2 (fr) | 2016-08-25 | 2018-03-01 | Northwestern University | Acides nucléiques sphériques micellaires obtenus à partir de matrices thermosensibles sans trace |
| ES2917000T3 (es) | 2016-10-24 | 2022-07-06 | Orionis Biosciences BV | Interferón-gamma mutante diana y usos del mismo |
| MA46770A (fr) | 2016-11-09 | 2019-09-18 | Agenus Inc | Anticorps anti-ox40, anticorps anti-gitr, et leurs procédés d'utilisation |
| US20190256603A1 (en) * | 2016-11-11 | 2019-08-22 | Medimmune, Llc | Anti-pd-l1 and anti-ctla-4 antibodies for treating non-small cell lung cancer |
| KR102642385B1 (ko) | 2017-02-06 | 2024-03-04 | 오리오니스 바이오사이언시스 엔브이 | 표적화된 키메라 단백질 및 이의 용도 |
| US10906985B2 (en) | 2017-02-06 | 2021-02-02 | Orionis Biosciences, Inc. | Targeted engineered interferon and uses thereof |
| US11433131B2 (en) | 2017-05-11 | 2022-09-06 | Northwestern University | Adoptive cell therapy using spherical nucleic acids (SNAs) |
| WO2018222949A1 (fr) | 2017-06-01 | 2018-12-06 | Cytomx Therapeutics, Inc. | Anticorps anti-pdl1 activables, et leurs procédés d'utilisation |
| US11285149B2 (en) | 2017-07-28 | 2022-03-29 | Dana-Farber Cancer Institute, Inc. | Enhanced immunotherapy of cancer using targeted transcriptional modulators |
| EA202091486A1 (ru) * | 2018-02-12 | 2021-02-08 | Кодиак Байосайенсес, Инк. | Способы и композиции для поляризации макрофагов |
| JPWO2019177159A1 (ja) * | 2018-03-15 | 2021-02-25 | 国立大学法人北海道大学 | 癌免疫療法併用剤 |
| SG11202010324TA (en) * | 2018-04-25 | 2020-11-27 | Medimmune Ltd | Formulations of human anti-pd-l1 antibodies |
| CN109675040B (zh) * | 2018-12-31 | 2021-07-30 | 清华大学 | 治疗乳腺癌的组合物及其应用 |
| CN113365659B (zh) * | 2019-01-31 | 2023-08-18 | 正大天晴药业集团股份有限公司 | 抗pd-l1抗体治疗头颈癌的用途 |
| EP3946300A4 (fr) * | 2019-04-02 | 2023-01-18 | Board of Regents, The University of Texas System | Combinaisons d'inhibiteurs de transcription et d'inhibiteurs de point de contrôle immunitaire pour traiter une maladie |
| US20220218693A1 (en) * | 2019-04-26 | 2022-07-14 | Kabushiki Kaisha Yakult Honsha | Immune checkpoint inhibitor combination therapy using quinoline carboxamide derivative |
| US20220354880A1 (en) * | 2019-09-30 | 2022-11-10 | Astrazeneca Ab | Combination treatment for cancer |
| WO2021072286A1 (fr) * | 2019-10-09 | 2021-04-15 | City Of Hope | Polythérapie pour le traitement du cancer utilisant des conjugués d'acides nucléiques anti-stat3 |
| US20220409642A1 (en) | 2019-11-04 | 2022-12-29 | Astrazeneca Ab | Combination therapy for treating cancer |
| AU2020398177A1 (en) * | 2019-12-05 | 2022-07-07 | Board Of Regents, The University Of Texas System | Exosomes-based therapy for liver fibrosis and other diseases associated with fibrosis |
| EP4149974A1 (fr) * | 2020-05-13 | 2023-03-22 | Institut National de la Santé et de la Recherche Médicale (INSERM) | Protéines recombinantes ayant des propriétés d'activation de ox40 |
| WO2022076596A1 (fr) * | 2020-10-06 | 2022-04-14 | Codiak Biosciences, Inc. | Constructions vésicules extracellulaires-oas ciblant stat6 |
| WO2023178141A2 (fr) * | 2022-03-15 | 2023-09-21 | Dicerna Pharmaceuticals, Inc. | Combinaison d'oligonucléotides de ciblage de stat3 et d'inhibiteurs de pd-l1 |
Family Cites Families (39)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4179337A (en) | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| JPS6023084B2 (ja) | 1979-07-11 | 1985-06-05 | 味の素株式会社 | 代用血液 |
| JPS5896026A (ja) | 1981-10-30 | 1983-06-07 | Nippon Chemiphar Co Ltd | 新規ウロキナ−ゼ誘導体およびその製造法ならびにそれを含有する血栓溶解剤 |
| US4640835A (en) | 1981-10-30 | 1987-02-03 | Nippon Chemiphar Company, Ltd. | Plasminogen activator derivatives |
| US4609546A (en) | 1982-06-24 | 1986-09-02 | Japan Chemical Research Co., Ltd. | Long-acting composition |
| US4496689A (en) | 1983-12-27 | 1985-01-29 | Miles Laboratories, Inc. | Covalently attached complex of alpha-1-proteinase inhibitor with a water soluble polymer |
| EP0206448B1 (fr) | 1985-06-19 | 1990-11-14 | Ajinomoto Co., Inc. | Hémoglobine liée à un poly(oxyde d'alkylène) |
| US4766106A (en) | 1985-06-26 | 1988-08-23 | Cetus Corporation | Solubilization of proteins for pharmaceutical compositions using polymer conjugation |
| EP0272253A4 (fr) | 1986-03-07 | 1990-02-05 | Massachusetts Inst Technology | Procede pour ameliorer la stabilite des glycoproteines. |
| US4791192A (en) | 1986-06-26 | 1988-12-13 | Takeda Chemical Industries, Ltd. | Chemically modified protein with polyethyleneglycol |
| WO1988007089A1 (fr) | 1987-03-18 | 1988-09-22 | Medical Research Council | Anticorps alteres |
| US5457035A (en) | 1993-07-23 | 1995-10-10 | Immunex Corporation | Cytokine which is a ligand for OX40 |
| US5821332A (en) | 1993-11-03 | 1998-10-13 | The Board Of Trustees Of The Leland Stanford Junior University | Receptor on the surface of activated CD4+ T-cells: ACT-4 |
| US6242566B1 (en) | 1994-02-10 | 2001-06-05 | Board Of Trustees Of The Leland Stanford Junior University | Ligand (ACT-4-L) to a receptor on the surface of activated CD4+ T-cells |
| US6312700B1 (en) | 1998-02-24 | 2001-11-06 | Andrew D. Weinberg | Method for enhancing an antigen specific immune response with OX-40L |
| EE05627B1 (et) | 1998-12-23 | 2013-02-15 | Pfizer Inc. | CTLA-4 vastased inimese monoklonaalsed antikehad |
| US7109003B2 (en) | 1998-12-23 | 2006-09-19 | Abgenix, Inc. | Methods for expressing and recovering human monoclonal antibodies to CTLA-4 |
| US7098192B2 (en) | 1999-04-08 | 2006-08-29 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotide modulation of STAT3 expression |
| US6159694A (en) | 1999-04-08 | 2000-12-12 | Isis Pharmaceuticals Inc. | Antisense modulation of stat3 expression |
| US7158164B2 (en) | 2003-08-29 | 2007-01-02 | Fuji Photo Film Co., Ltd. | Thermal development method and apparatus |
| JP5379347B2 (ja) | 2003-09-18 | 2013-12-25 | アイシス ファーマシューティカルズ， インコーポレーテッド | ４’−チオヌクレオシドおよびオリゴマー化合物 |
| SI1877090T1 (sl) | 2005-05-06 | 2014-12-31 | Providence Health System | Trimerni fuzijski protein OY40-imunoglobulina in postopki uporabe |
| CN104356236B (zh) | 2005-07-01 | 2020-07-03 | E.R.施贵宝&圣斯有限责任公司 | 抗程序性死亡配体1(pd-l1)的人单克隆抗体 |
| US20070243184A1 (en) | 2005-11-08 | 2007-10-18 | Steven Fischkoff | Prophylaxis and treatment of enterocolitis associated with anti-ctla-4 antibody therapy |
| DK2066684T3 (da) | 2006-05-11 | 2012-10-22 | Isis Pharmaceuticals Inc | 5´-Modificerede bicycliske nukleinsyreanaloge |
| US20100190837A1 (en) | 2007-02-15 | 2010-07-29 | Isis Pharmaceuticals, Inc. | 5'-Substituted-2-F' Modified Nucleosides and Oligomeric Compounds Prepared Therefrom |
| WO2008109494A1 (fr) | 2007-03-02 | 2008-09-12 | Mdrna, Inc. | Composés d'acides nucléiques conçus pour inhiber l'expression du gène stat3 et utilisations de ceux-ci |
| EP2190994A2 (fr) | 2007-09-17 | 2010-06-02 | Intradigm Corporation | Compositions comprenant des arnsi de stat3 et leurs procédés d'utilisation |
| WO2009089149A1 (fr) | 2008-01-03 | 2009-07-16 | The Johns Hopkins University | Antagonistes de b7-h1 (cd274) induisant l'apoptose de cellules tumorales |
| AU2009296392B2 (en) | 2008-09-26 | 2016-06-02 | Dana-Farber Cancer Institute, Inc. | Human anti-PD-1, PD-L1, and PD-L2 antibodies and uses therefor |
| PE20120341A1 (es) | 2008-12-09 | 2012-04-24 | Genentech Inc | Anticuerpos anti-pd-l1 y su uso para mejorar la funcion de celulas t |
| WO2010089411A2 (fr) | 2009-02-09 | 2010-08-12 | Universite De La Mediterranee | Anticorps pd-1 et anticorps pd-l1 et leurs utilisations |
| KR101573109B1 (ko) | 2009-11-24 | 2015-12-01 | 메디뮨 리미티드 | Ｂ７―ｈ１에 대한 표적화된 결합 물질 |
| HUE042173T2 (hu) | 2011-04-01 | 2019-06-28 | Ionis Pharmaceuticals Inc | 'Signal transducer and activator of transcription 3' (stat3) expresszió modulálása |
| CA2833636A1 (fr) | 2011-04-20 | 2012-10-26 | Amplimmune, Inc. | Anticorps et autres molecules qui se lient a b7-h1 et a pd-1 |
| EP2812022B1 (fr) | 2012-02-06 | 2019-06-26 | Providence Health & Services - Oregon | P0rocédés de surveillance le traitement du cancer utilisant des agonistes de ox40 |
| JP2015508816A (ja) | 2012-03-02 | 2015-03-23 | プロビデンス ヘルス アンド サービシーズ−オレゴン | Ｏｘ４０アゴニスト／ｉｌ−２二重癌治療法 |
| CA2866707A1 (fr) * | 2012-03-07 | 2013-09-12 | H. Lee Moffitt Cancer Center And Research Institute, Inc. | Inhibiteurs selectifs d'histone desacetylase 6 |
| EP3483273A1 (fr) | 2012-10-31 | 2019-05-15 | Ionis Pharmaceuticals, Inc. | Traitement du cancer |
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- 2015-10-20 WO PCT/EP2015/074271 patent/WO2016062722A1/fr active Application Filing
- 2015-10-20 DK DK15784628.8T patent/DK3209778T3/da active
- 2015-10-20 AU AU2015335029A patent/AU2015335029B2/en active Active
- 2015-10-20 SG SG11201703219WA patent/SG11201703219WA/en unknown
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- 2015-10-20 EP EP15784628.8A patent/EP3209778B1/fr active Active
- 2015-10-20 PL PL15784628T patent/PL3209778T3/pl unknown
- 2015-10-20 CA CA2965034A patent/CA2965034C/fr active Active
- 2015-10-20 EP EP19166017.4A patent/EP3550019A1/fr active Pending
- 2015-10-20 HU HUE15784628A patent/HUE043227T2/hu unknown
- 2015-10-20 RU RU2017117664A patent/RU2744841C2/ru active
- 2015-10-20 CN CN202211353077.8A patent/CN115920007A/zh active Pending
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- 2015-10-20 KR KR1020177013607A patent/KR20170072928A/ko active Application Filing
- 2015-10-20 US US15/521,185 patent/US20190194654A1/en not_active Abandoned
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2017
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2022
- 2022-10-13 US US18/046,173 patent/US20230374503A1/en active Pending
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|---|---|
| CN107106590A (zh) | 2017-08-29 |
| RU2744841C2 (ru) | 2021-03-16 |
| DK3209778T3 (da) | 2019-05-27 |
| SG11201703219WA (en) | 2017-05-30 |
| SG10202105879XA (en) | 2021-07-29 |
| AU2015335029A1 (en) | 2017-05-18 |
| JP6687612B2 (ja) | 2020-04-22 |
| US20230374503A1 (en) | 2023-11-23 |
| WO2016062722A1 (fr) | 2016-04-28 |
| PL3209778T3 (pl) | 2019-08-30 |
| RU2017117664A (ru) | 2018-11-26 |
| KR20230128139A (ko) | 2023-09-01 |
| EP3209778A1 (fr) | 2017-08-30 |
| CN115920007A (zh) | 2023-04-07 |
| RU2017117664A3 (fr) | 2019-05-23 |
| TR201906415T4 (tr) | 2019-05-21 |
| ES2727154T3 (es) | 2019-10-14 |
| EP3550019A1 (fr) | 2019-10-09 |
| WO2016062722A8 (fr) | 2017-03-09 |
| JP2017537070A (ja) | 2017-12-14 |
| CA2965034C (fr) | 2023-05-02 |
| CN107106590B (zh) | 2022-10-18 |
| US20190194654A1 (en) | 2019-06-27 |
| IL304663A (en) | 2023-09-01 |
| EP3209778B1 (fr) | 2019-04-03 |
| HUE043227T2 (hu) | 2019-08-28 |
| IL251813A0 (en) | 2017-06-29 |
| KR20170072928A (ko) | 2017-06-27 |
| AU2015335029B2 (en) | 2021-09-23 |
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